US 9,168,568 B2Granted

Particle manipulation system with cytometric confirmation

AssigneeOwl biomedical, Inc.

InventorsJohn S Foster, Nicholas C. Martinez, Kevin E. Shields, Jaquelin K. Spong

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Abstract

A MEMS-based particle manipulation system which uses a particle manipulation stage and a plurality of laser interrogation regions. The laser interrogation regions may be used to assess the effectiveness or accuracy of the particle manipulation stage. In one exemplary embodiment, the particle manipulation stage is a microfabricated valve, which sorts a target particle from non-target particles in a fluid stream. The laser interrogation stages are disposed in the microfabricated fluid channels at the input and output of the valve. By reversing the flow from output to input, the same laser interrogation region may be used to perform the cytometry. The cytometry may be performed throughout the sorting process to optimize or control the sorting, or may be performed afterward to allow a multi-pass, sequential sort to be performed on the same sample.

Claims22

Dependent claims

A particle manipulation system, comprising:

a sample channel, a sort channel and a waste channel in fluid communication with one another and formed in a surface of a substrate, wherein a flow in the sample channel is substantially parallel to the surface, and wherein the sample channel flows to at least one of the sort channel and the waste channel when the flow is forward;
an interrogation means disposed in the sample channel, wherein target particles provide detection signals;
a microfabricated particle sorting mechanism which moves in a plane parallel to the surface, and directs the target particles from the sample channel into the waste channel when the microfabricated particle sorting mechanism is in a first position, and which directs the other particles into the sort channel when in a second position;
and
a fluid control means for controlling a direction and rate of fluid flow in the channels, wherein the fluid control means reverses the flow from at least one of the sort channel and the waste channel back to the sample channel, such that the fluid passes through the interrogation region and the microfabricated particle sorting mechanism a plurality of times
and wherein the microfabricated particle sorting mechanism moves from the first position to the second position in response to a force, and wherein the motion is substantially in a plane parallel to the surface of the substrate and wherein at least one of the sort channel and the waste channel is substantially orthogonal to the surface and directly below at least a portion of the microfabricated particle sorting mechanism over at least a portion of its motion.

3 more elements

A method for manipulation particles in a fluid, comprising:

providing a sample stream, a sort stream, and a waste stream, all connected by microfluidic channels formed on the surface of a substrate, wherein the sample stream flows from a sample reservoir to at least one of a sort reservoir and a waste reservoir when a flow is forward;
disposing an interrogation means in the sample stream, wherein target particles provide a detection signal when passing through the interrogation means in a first interrogation period;
providing a microfabricated particle sorting mechanism at a junction of the sort stream and the waste stream, wherein the microfabricated particle sorting mechanism moves in a plane parallel to the surface, and wherein at least one of the sort stream and the waste stream is substantially orthogonal to the surface;
and wherein the microfabricated particle sorting mechanism moves from the first position to the second position in response to a force, and wherein the motion is substantially in a plane parallel to the surface of the substrate and wherein at least one of the sort channel and the waste channel is substantially orthogonal to the surface and directly below at least a portion of the microfabricated particle sorting mechanism over at least a portion of its motion,
directing the target particles from the sample stream into the sort reservoir based on the detection signal, and directing the other particles into the waste reservoir to sort the particles in a first sorting period;
and
reversing the flow from at least one of the sort reservoir and the waste reservoir back to the sample stream, to form a reversed stream which flows back through the interrogation means and the microfabricated particle sorting mechanism.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/104,084Filed 12 Dec 2013 · continuation in part
Priority: 1 Aug 2012
Published: US 2014/0034555 A110 Apr 2014
Granted: 27 Oct 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

B07C 5/34
Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or…:…
B01L 3/502761
By integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g.…
G01N 15/1404
Optical investigation techniques, e.g. flow cytometry: handling flow, e.g. hydrodynamic focusing
G01N 15/1434
Optical investigation techniques, e.g. flow cytometry: optical arrangements

Family

Application13/507,830Parent of this continuation-in-part · filed 1 Aug 2012
US 2014/0097129 A1Pre-grant publication · published 10 Apr 2014
US 2014/0034555 A1Published application
US 9,194,786 B2Related patent
US 9,168,568 B2This patent

From the US filing history. Foreign family members aren’t listed.